Ep. 513 Combination Therapy and Clinical trials for Advanced HCC: What They Really Mean

In the past five years, the use of immunotherapeutic agents for advanced cancers has emerged as a promising alternative to tyrosine kinase inhibitors and chemotherapy, making it an exciting time to be practicing oncology. In this episode, Dr. Tyler Sandow interviews oncology experts about the landscape of advanced hepatocellular carcinoma (HCC) and the current state of immunotherapy treatments. He is joined by medical oncologists Dr. Jonathan Mizrah, Dr. Lingling Du, and Dr. Adam Burgoyne, as well as interventional oncologist Dr. Zachary Berman. Physicians, nurses, nurse practitioners, and physician assistants can follow this link to earn CME / CE credits for completing an accredited learning activity related to this discussion: https://www.cmeuniversity.com/course/take/125737 --- This podcast is supported by an educational grant from AstraZeneca Pharmaceuticals and Boston Scientific. --- SYNPOSIS Drs. Burgoyne and Mizrahi provide a primer on immunotherapy and explain how they communicate the principles of this treatment to their patients. Dr. Du discusses the Imbrave clinical trial and how recent studies have shown improved overall survival when immunotherapeutic agents are used, especially when multiple agents targeting various pathways are employed. When choosing between different regimens, the doctors consider factors such as the patient's underlying liver function, symptom burden, and prior treatments. Importantly, the doctors also discuss contraindications to immunotherapy, including a history of organ transplant, autoimmune disease, and poor performance status—all of which put patients at high risk for deterioration with this treatment. The treatment of patients with poor liver function remains controversial, as underlying cirrhosis may prevent the recovery of liver function. Dr. Berman outlines recent clinical trials studying the effects of transarterial chemoembolization (TACE) combined with immunotherapy. Finally, the doctors discuss the future of HCC treatment and the benefits of continued innovation in both interventional and medical oncology. --- TIMESTAMPS 00:00 - Introduction to Immunotherapy 04:32 - Notable Clinical Trials 13:39 - HCC Etiology and Immunotherapy Outcomes 18:43 - Contraindications for Immunotherapy 23:05 - Adverse Effects from Treatment 25:14 - Combination Therapy 36:22 - Considerations for Immunotherapy Dosing 40:26 - The Future of HCC Treatment --- RESOURCES Atezolizumab plus Bevacizumab in Unresectable Hepatocellular Carcinoma, IMbrave150 Trial (Finn et al, 2020): https://pubmed.ncbi.nlm.nih.gov/32402160/ Tremelimumab plus Durvalumab in Unresectable Hepatocellular Carcinoma, HIMALAYA Trial (Abou-Alfa et al, 2022): https://evidence.nejm.org/doi/full/10.1056/EVIDoa2100070 Nivolumab versus sorafenib in advanced hepatocellular carcinoma (CheckMate 459): a randomised, multicentre, open-label, phase 3 trial (Yau, 2022): https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(21)00604-5/abstract Nivolumab (NIVO) plus ipilimumab (IPI) vs lenvatinib (LEN) or sorafenib (SOR) as first-line treatment for unresectable hepatocellular carcinoma (uHCC): First results from CheckMate 9DW (Galle, 2024): https://ascopubs.org/doi/10.1200/JCO.2024.42.17_suppl.LBA4008 Randomized Phase 3 LEAP-012 Study: Transarterial Chemoembolization With or Without Lenvatinib Plus Pembrolizumab for Intermediate-Stage Hepatocellular Carcinoma Not Amenable to Curative Treatment (Llovet, 2022): https://pubmed.ncbi.nlm.nih.gov/35119481/ EMERALD-1: A phase 3, randomized, placebo-controlled study of transarterial chemoembolization combined with durvalumab with or without bevacizumab in participants with unresectable hepatocellular carcinoma eligible for embolization (Lencioni, 2024): https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.LBA432 CME Accreditation Information: https://f7cae4ec-b69e-490d-9e0f-19b16a6f146d.usrfiles.com/ugd/f7cae4_a7c37ea3cd1b4d3fa53d5edf8dfe255b.pdf